The purpose of this project is to determine the incidence rates, rates of progression, and risk factors for the chronic complications of NIDDM. The study is conducted in the Pima Indians of the Gila River Indian Community, who have participated in a longitudinal epidemiologic study since 1965 (see project Z01 DK 69000). Risk factors for the major complications of diabetes, retinopathy, nephropathy, and coronary artery disease, are determined by longitudinal follow-up of diabetic subjects. Methods of ascertainment of these complications include fundus photography, measurement of urine albumin and serum creatinine concentrations, and electrocardiography. Not only is the familial pattern of type 2 diabetes in the Pima Indians consistent with an effect of a major gene, but so is the pattern of diabetic nephropathy among the diabetic subjects. Statistical modeling of the risk of nephropathy as a function of duration of diabetes suggests the importance of a single gene. Linkage analyses among those persons who were part of a genome-wide linkage study (see project # Z01 DK 69028-09 PECR) suggest two possible locations for such a gene. It is hypothesized that one gene may influence ultimate susceptibility to nephropathy and the other the duration of diabetes necessary for its appearance. Despite the suggestion of genetic determinants of diabetic nephropathy, this complication is clearly influenced by a large number of factors. We have recently found that low concentrations of HDL cholesterol predict the onset of the early stages of nephropathy ("micro-albuminuria") in Pima women, but not men. Data from the Pima Indian study on the relationship between 2-hour post-load plasma glucose and complications have previously been very influential in the selection of internationally-accepted diagnostic criteria for diabetes. These observations have recently been expanded to include fasting plasma glucose and glycohemoglobin, and confirmatory findings have been made in other populations.